Factor VIII plays an important role in the coagulation cascade responsible for hemostasis and is related to both hemophilia A and von Willebrand's disease (vWd). Reduced levels of F.VIII related antigen (VIIIR:Ag) are seen in vWd but not in hemophilia. This antigen is produced by the vascular endothelial cells and has been thought to play a role in atherosclerosis. Endothelial cells in culture continue to produce VIIIR:Ag ex vivo. We propose to study the genetics of this factor by fusing human endothelial cells in culture with heterologous cells which do no express this antigen but are compatible with its expression. Viable hybrid cells which result from fusion will be isolated and assayed for VIIIR:Ag by immunofluorescence. Such hybrids usually retain the complete heterologous genome, but only incomplete human chromosome sets. Only some of the hybrids are expected to retain the human chromosome(s) required for expression of VIIIR:Ag. The correlation between this factor and a particular chromosome will be established by identifying isozyme markers of each of the human chromosomes contained in hybrid cells that express VIIIR:Ag, and in hybrids that do not express it. We have found that certain non-endothelial cells suppress the expression of VIIIR:Ag in endothelial cell hybrids, but not in mixed cultures. The nature of such intracellular regulation will be investigated.